Although much is known about the biology of Francisella tularensis, the factors that regulate its natural prevalence remain un-described. We seek to test the 'rule of the incumbent' hypothesis: by analogy with politics, F. tularensis epizootics in the northeastern United States are limited by interactions with a 'ruling' endosymbiotic Francisella sp. (previously classified as Wolbachia sp.) common within tissues of dog ticks, Dermacentor variabilis. The recent outbreak of tularemia on Martha's Vineyard provides a unique opportunity for identifying factors that serve as the basis for increased transmission of this rare infection because sites there appear to be longstanding natural foci of this infection. However, testing this hypothesis requires identification of these natural foci, which may comprise small patches of vegetation; transmission is not homogeneously distributed over the entire 100,000-hectare island. Accordingly, we first seek to identify such natural foci by (1) determining whether striped skunks (Mephitis mephitis) serve as effective sentinels for F. tularensis transmission; and (2) complementing skunk-based predictions by enlisting landscapers and others who are occupationally exposed to tularemia and other tick borne infections to actively report, in real time, the presence of animal carcasses encountered during their work. Natural foci will be definitively confirmed by intensive longitudinal epizootiologic analyses (prevalence of F. tularensis infection in ticks and other potential vector arthropods; evidence of exposure in rodents and other animals). In this manner, we shall accumulate reliable study sites and the preliminary data required for a comprehensive test of the 'rule of the incumbent' hypothesis. In addition, our mapping of risky sites may serve as the basis for local public health measures. We anticipate that the epidemiologic and epizootiologic methods developed or validated during the proposed work may contribute towards enhanced investigations of tularemia outbreaks; new prevention strategies for those at risk of natural or illicit tularemia exposure; enhanced detection of F. tularensis in the environment; and, ultimately, a better understanding of F. tularensis-host interactions.